transformation was accomplished in one pot. (10) Because the reaction creates two new bonds with a moderately high degree of stereocontrol, it represents a highly convergent synthetic method. Experimental conditions and procedure Typical conditions Organometallic nucleophiles used for conjugate additions are most often prepared in situ. The use of anhydrous equipment and inert atmosphere is necessary. Because these factors are sometimes difficult to control and the strength of freshly prepared reagents can vary substantially, titration methods are necessary to verify the purity of reagents. A number of efficient titration methodologies exist. Usually, vicinal difunctionalizations are carried out in one pot, without the intermediacy of a neutral protected enolate. However, in specific cases it may be necessary to protect the intermediate of β-addition. Before reaching this point, however, solvent and nucleophile screens, order of addition adjustments, and counterion adjustments can be made to optimize the one-pot process for a particular combination of carbonyl compound, nucleophile, and alkylating (or acylating) agent. Solvent adjustments between the two steps are common; if one solvent is used, tetrahydrofuran is the solvent of choice. Polar aprotic solvents should be avoided for the conjugate addition step. Concerning temperature, conjugate additions are usually carried out at low temperatures (-78 °C), while alkylations are carried out at slightly higher temperatures (0 to -30 °C). Less reactive alkylating agents may require room temperature. Example procedure (11) To 6.25 g (50 mmol) of 4,4-dimethyl-2-cyclohexen-1-one and 0.5 g (5.6 mmol) of cuprous cyanide in 400 mL of diethyl ether at –23° under argon was added 100 mL (~0.75 M in diethyl ether) of 5-trimethylsilyl-4-pentynylmagnesium iodide during 4 hours. Methyl chloroformate (8 mL, 100 mmol) was added and stirring continued for 1 hour at –23° and 0.5 hour at room temperature. Hydrochloric acid (100 mL, 2.0 M) then was added and the organic phase separated and dried with magnesium sulfate. The solvent was removed and the residue chromatographed on silica gel using 5% diethyl ether–petroleum ether to give methyl 3,3-dimethyl-6-oxo-2-[5-(trimethylsilyl)-4-pentynyl]cyclohexanecarboxylate, 9.66 g (60%). IR 2000, 2140, 1755, 1715, 1660, 1615, 1440, 1280, 1250, 1225, 1205, and 845 cm–1; 1H NMR ( CDCl3) δ 0.13 (s, 9H), 0.93 (s, 3H), 1.02 (s, 3H), 1.2–2.3 (m, 11H), 3.74 (s, 3H). Anal. Calc. for C18H30O3Si: C, 67.05; H, 9.4. Found: C, 67.1; H, 9.65. References Organic reactions